The identification of the etiologies of frailty and age-related vulnerability remains one of the most important challenges in Gerontologic research. Key to this challenge is the development of a better understanding of the underlying biological basis that contributes to frailty, and the identification of key biological pathways for the development of interventions that might help prevent or alleviate frailty and loss of independence. The purpose of Johns Hopkins Older Americans Independence Center (OAIC) Biological Mechanisms Core (RC- 2) is to provide access to a broad array of state of the art biological measurement resources that will enable the next generation of frailty-focused discovery. In addition, RC2 will provide biological samples, and facilitate training, mentorship and translation around biological mechanisms that impact the development of frailty and declines in independence. The specific aims of RC2 are 1) to provide state of the art scientific expertise, infrastructure, and technology necessarily to forward biological and etiological research related to frailty, 2) to provide access to biological samples from human subjects and from animal models necessary to test hypotheses related to frailty, 3) to facilitate the translation of biological findings into interventions or prevention focused clinical studies, 4) to provide training, mentorship, and guidance to promising junior investigators around biological mechanisms that impact frailty, and 5) to provide institutional and external visibility for RC-2 related science and activities, the human resources, infrastructure, and training necessary to facilitate the highest quality genetic and molecular studies related to frailty, the overall focus of the Hopkins OAIC. These aims will be accomplished through close collaboration between the interdisciplinary core leaders and their laboratories, the leadership of the other OAIC cores, and through the engagement of highly expert consultants in the highly relevant areas of epigenetic, telomere biology, mitochondrial function, mouse model development, and nanotechnologies and proteomics. By providing these resources, RC-2 will foster high quality research that elucidate clinically relevant biological pathways that underlie frailty, and related interventions that attenuate frailty and loss of independence.